Therapeutic benefit or "effectiveness" in oncology trials, as well as in most current (New) Phase I trials, is multi-faceted.
The final indication that Phase I trials have moved from only testing toxicity to testing both toxicity and efficacy is reflected by the altered purpose of Phase I trials.
(102) Thus, New Phase I trials must produce enough efficacy data to allow the FDA to grant access to drugs following this phase of the trials.
(121) However, investigational drugs have increasingly become available during and at the conclusion of Phase I trials. (122) The 2006 D.C.
Circuit vacated this decision in November 2006 (124) and the same court, in an en banc decision, held in August 2007 that there is no fundamental right of access to experimental drugs for terminally ill individuals, (125) the original decision and debate surrounding the decision illustrates a growing view that it is safe and effective to provide INDs that have only been tested in Phase I trials to patients outside of clinical trials.
The FDA's accelerated approval processes illustrate the ways in which Phase I trials have changed over time becoming similar to Phase II trials.
drugs are safe and effective," (136) current Phase I trials must provide enough data on therapeutic effects so that the INDs can be made available to patients in an ethical and reasonable manner.
Given the shift from Traditional Phase I to New Phase I trials resulting from the expansion of patient populations and modification of trial designs, and the subsequent accelerated approval processes granting early access to non-approved INDs, the FDA must adapt the framework surrounding the entire clinical trial process to account for these changes.
As a first step, the FDA can draft a guidance document distinguishing Traditional from New Phase I trials and impose heightened regulations only on New Phase I trials that test efficacy.
First, the FDA can leave the current Phase system in place, but impose the same regulatory framework on Phase I trials that is imposed on Phases II and III because Phase II and III trials test for efficacy and safety, and utilize ill patients.
Drafting a Suggestive Guidance Document Distinguishing "New'" from "Traditional" Phase I Trials
As a first step in determining which protocols and regulations should be applied to New Phase I trials, the FDA should draft a guidance document that: 1) distinguishes Phase I trials that test safety and efficacy (New Phase I Trials) from those Traditional Phase I trials that only test safety; and 2) places appropriate protocols and regulations on each trial.